Proteinopathies are a family of human disease caused by toxic aggregation-prone
proteins and featured by the presence of
protein aggregates in the affected cells. The
ubiquitin-
proteasome system (UPS) and autophagy are two major intracellular protein degradation pathways. The UPS mediates the targeted degradation of most normal
proteins after performing their normal functions as well as the removal of abnormal, soluble
proteins. Autophagy is mainly responsible for degradation of defective organelles and the bulk degradation of cytoplasm during
starvation. The collaboration between the UPS and autophagy appears to be essential to
protein quality control in the cell. UPS proteolytic function often becomes inadequate in
proteinopathies which may lead to activation of autophagy, striving to remove abnormal
proteins especially the aggregated forms. HADC6, p62, and FoxO3 may play an important role in mobilizing this proteolytic consortium. Benign measures to enhance
proteasome function are currently lacking; however, enhancement of autophagy via pharmacological intervention and/or lifestyle change has shown great promise in alleviating bona fide
proteinopathies in the cell and animal models. These pharmacological interventions are expected to be applied clinically to treat human
proteinopathies in the near future.